trans-Resveratrol is a natural bioactive compound with well-recognized health promoting effects. When exposed to UV light, this compound can undergo a photochemically induced trans/cis isomerization and a 6π electrochemical cyclization with the subsequent formation of 2,4,6-trihydroxyphenanthrene (THP). THP is a potentially harmful compound which can exert genotoxic effects. In this work we improved the chromatographic separation and determination of the two resveratrol isomers and of THP by using a non-commercial pentafluorophenyl stationary phase. We assessed the effect of natural deep eutectic solvents (NaDES) as possible photo-protective agents by evaluating cis-resveratrol isomer and THP formation under different UV-light exposure conditions with the aim of enhancing resveratrol photostability and inhibiting THP production. Our results demonstrate a marked photoprotective effect exerted by glycerol-containing NaDES, and in particular by proline/glycerol NaDES, which exerts a strong inhibitory effect on the photochemical isomerization of resveratrol and significantly limits the formation of the toxic derivative THP. Considering the presence of resveratrol in various commercial products, these results are of note in view of the potential genotoxic risk associated with its photochemical degradation products and in view of the need for the development of green, eco-sustainable and biocompatible resveratrol photo-stable formulations.
Antibiotic resistance poses a serious threat to the current healthcare system, negatively impacting the effectiveness of many antimicrobial treatments. The situation is exacerbated by the widespread overuse and abuse of available antibiotics, accelerating the evolution of resistance. Thus, there is an urgent need for novel approaches to therapy to overcome established resistance mechanisms. Plants produce molecules capable of inhibiting bacterial growth in various ways, offering promising paths for the development of alternative antibiotic medicine. This review emphasizes the necessity of research efforts on plant-derived chemicals in the hopes of finding and creating novel drugs that can successfully target resistant bacterial populations. Investigating these natural chemicals allows us to improve our knowledge of novel antimicrobial pathways and also expands our antibacterial repertoire with novel molecules. Simultaneously, it is still necessary to utilize present antibiotics sparingly; prudent prescribing practices must be encouraged to extend the effectiveness of current medications. The combination of innovative drug research and responsible drug usage offers an integrated strategy for managing the antibiotic resistance challenge.
Alzheimer's disease (AD) is a neurodegenerative disorder whose main pathological hallmark is the accumulation of Amyloid-beta peptide (A beta) in the form of senile plaques. A beta can cause neurodegeneration and disrupt cognitive functions by several mechanisms, including oxidative stress. ERp57 is a protein disulfide isomerase involved in the cellular stress response and known to be present in the cerebrospinal fluid of normal individuals as a complex with A beta peptides, suggesting that it may be a carrier protein which prevents aggregation of A beta. Although several studies show ERp57 involvement in neurodegenerative diseases, no clear mechanism of action has been identified thus far. In this work, we gain insights into the interaction of A beta with ERp57, with a special focus on the contribution of ERp57 to the defense system of the cell. Here, we show that recombinant ERp57 directly interacts with the A beta(25-35) fragment in vitro with high affinity via two in silico-predicted main sites of interaction. Furthermore, we used human neuroblastoma cells to show that short-term A beta(25-35) treatment induces ERp57 decrease in intracellular protein levels, different intracellular localization, and ERp57 secretion in the cultured medium. Finally, we demonstrate that recombinant ERp57 counteracts the toxic effects of A beta(25-35) and restores cellular viability, by preventing A beta(25-35) aggregation. Overall, the present study shows that extracellular ERp57 can exert a protective effect from A beta toxicity and highlights it as a possible therapeutic tool in the treatment of AD.
Oleacein (Olea) and Oleocanthal (Oleo) are two phenolic compounds found in olive oil. Cell and animal studies have shown these two compounds can modulate inflammation, cancer, and neurodegenerative diseases. Unfortunately, the study of the pharmacokinetics of these two compounds appears difficult due to their high reactivity with primary amines. Indeed, the presence of primary amines in culture media and biological fluids raises the question as to whether the observed biological effects are attributable to the parent compounds or to their amine derivatives. In the present work, we investigated the adduct formation between Olea or Oleo and tris(hydroxymethyl)aminomethane (Tris), a well-known primary amine used primarily as a buffer system, showing that the reaction kinetics were extremely rapid. In addition, we assessed whether the newly formed Tris adducts, i.e., Olea-Tris and Oleo-Tris, retained their antioxidant capacity by means of the ABTS and DPPH radical scavenging assays, showing that their activity was partially maintained. Finally, we evaluated the anti-inflammatory activity of these adducts on murine BV-2 microglial cells stimulated with lipopolysaccharide (LPS) and kept in an amine-free culture medium, showing how the biological response varied as the compound was degraded. Taken together, these data demonstrate that the biological effects reported in the literature are mainly due to the amino-derivatives of Olea and Oleo rather than the polyphenols derived from their breakdown (tyrosol and hydroxytyrosol).
The novel amphiphilic polyacrylate grafted with cholesterol moieties, PAAbCH, previously synthesized, was deeply characterized and investigated in the lab and on a pre-industrial scale. Solid-state NMR analysis confirmed the polymer structure, and several water-based pharmaceutical and cosmetic products were developed. In particular, stable oil/water emulsions with vegetable oils, squalene, and ceramides were prepared, as well as hydrophilic medicated films loaded with diclofenac, providing a prolonged drug release. PAAbCH also formed polyelectrolyte hydrogel complexes with chitosan, both at the macro- and nano-scale. The results demonstrate that this polymer has promising potential as an innovative excipient, acting as a solubility enhancer, viscosity enhancer, and emulsifying agent with an easy scale-up transfer process.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by beta-amyloid (Aβ) deposition, hyperphosphorylation of tau protein (pTau), mitochondrial impairment and neuroinflammation. Several risk factors, such as aging, genetics, cardiovascular diseases (CVD) and lifestyle, concur to the onset of the disease. Among modifiable risk factors, micronutrient intake has gained attention for its potential role in preventing or slowing down disease progression. In this narrative review, we summarize current evidence linking vitamin deficiencies to the onset and progression of AD. We analyze evidence for fat-soluble (A, D, E, K) and water-soluble vitamins (C and B-complex, both canonical B1–B12 and non-canonical forms such as B13, B15, and B17). We then analyze individual and combinational vitamin supplementation in AD patients as the primary focus, with additional data derived from animal and cellular studies when human data are limited. As final result, B6, B9, and B12 vitamins have demonstrated promising effects in clinical trials. Interestingly, some beneficial effects have also been observed in the prodromal stage of AD when these vitamins were combined with antioxidant compounds such as vitamin C and vitamin E. Given the multifactorial nature of AD, targeting isolated vitamin deficiencies may not be sufficient. Future research should focus on long-term clinical trials (at least 2 years), particularly exploring combinations of vitamins and antioxidants, to achieve meaningful therapeutic effects. This review is intended as a point of support for future clinical trials in the treatment of AD from a nutritional point of view.